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From Pediatric to Adult Brain Cancer: Exploring Histone H3 Mutations in Australian Brain Cancer Patients.
Benedicte Grebstad Tune1,2,3, Heena Sareen3,4, Branka Powter3
1Department of Pediatric Research, Division of Paediatric and Adolescent Medicine, Oslo University Hospital Rikshospitalet, 0372 Oslo, Norway.
Biomedicines
|November 25, 2023
Summary
Histone mutations (H3.3-K27M, H3.3-G34R, H3.1-K27M) are key in pediatric brain cancers. New droplet digital PCR assays detect these mutations in cell-free DNA and CSF, but were not found in adult gliomas, except for H3.3-G34R in one case.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Genetic histone variants, particularly histone 3 (H3) family mutations, are linked to cancer development and progression.
- H3.1 and H3.3 mutations are primarily associated with pediatric brain cancers and serve as poor prognostic biomarkers in children.
- Recent research suggests potential roles for H3 alterations in adult brain cancers.
Purpose of the Study:
- To establish reliable droplet digital PCR (ddPCR) assays for detecting three specific histone mutations (H3.3-K27M, H3.3-G34R, H3.1-K27M) associated with childhood brain cancer.
- To evaluate the utility of these ddPCR assays for detecting histone mutations in cell-free DNA (cfDNA) and cerebrospinal fluid (CSF).
- To screen adult glioma and diffuse hemispheric glioma patient tumor tissues for these three histone mutations.
Main Methods:
- Development and validation of droplet digital PCR (ddPCR) based assays.
- Detection of histone mutations in cell-free DNA from cultured diffuse intrinsic pontine glioma (DIPG) cells and CSF from a pediatric DIPG patient.
- Screening of tumor tissue DNA from 89 adult glioma patients and 1 adult diffuse hemispheric glioma patient.
Main Results:
- The established ddPCR assays successfully detected histone mutations in cfDNA and CSF samples from DIPG cases.
- No histone mutations (H3.3-K27M, H3.3-G34R, H3.1-K27M) were detected in the tumor tissue DNA of 89 adult glioma patients.
- The H3.3-G34R mutation was confirmed in the tumor tissue of the single adult diffuse hemispheric glioma patient screened.
Conclusions:
- Droplet digital PCR provides a sensitive method for detecting key histone mutations in cfDNA and CSF, relevant for pediatric brain cancers.
- The screened histone mutations (H3.3-K27M, H3.3-G34R, H3.1-K27M) appear to be rare in adult gliomas from the studied population.
- The presence of H3.3-G34R in one adult diffuse hemispheric glioma case warrants further investigation into H3 mutations in adult brain tumors.
